甲基莲心碱在大鼠肝脏中的代谢产物及其途径  

Metabolic products and pathway of neferine in rat liver

作　　者：黄颖[1] 赵立波[1] 李帅[1] 刘萍[1] 胡本容[1] 王嘉陵[1] 向继洲[1] 

机构地区：[1]华中科技大学同济医学院药理学教研室,湖北武汉430030

出　　处：《药学学报》2007年第10期1034-1040,共7页Acta Pharmaceutica Sinica

摘　　要：大鼠灌胃给予甲基莲心碱20 mg.kg-1,采用液相色谱-串联质谱联用法对大鼠肝脏中的代谢产物进行分析;并建立肝微粒体温浴及NADPH再生体系,采用高效液相色谱-紫外检测法研究CYP450亚型的特异性抑制剂对甲基莲心碱体外代谢的影响。在正离子检测方式下,除甲基莲心碱外共检测到4种代谢产物M1、M2(主要代谢产物)、M3和M4。其中,M2和M4通过与对照品的色谱和质谱比对,确认为莲心碱和异莲心碱,而M1和M3可能为去甲基莲心碱和去甲基异莲心碱。CYP3A1的特异性抑制剂酮康唑和CYP2D1的特异性抑制剂奎尼丁均可抑制甲基莲心碱在肝微粒体温孵液中的代谢,其主要代谢产物莲心碱的生成抑制率分别为25.7%和80.5%。因此提示,甲基莲心碱在肝脏中的主要代谢途径是苄基和喹啉环上的甲氧基脱甲基化,其主要代谢物为莲心碱,CYP2D1和CYP3A1均参与了其生物转化。The present study utilized LC-MS and HPLC approaches to characterize the metabolites of neferine in rat liver after an oral administration of 20 mg . kg^-1, and investigated the involvement of CYP450 isoforms in the metabolism of neferine by their selective inhibitors in vitro, separately. In positive ionization mode, besides neferine, four metabolites （M1 -M4） were detected. M2 （the major metabolite） and M4 were identified as liensinine and isoliensinine by comparison with reference substances. Moreover, according to the analysis of metabolic rule of parent drug （ neferine）, M1 and M3 may be desmethyl- liensinine and desmethyl-isoliensinine, respectively. Furthermore, the metabolism of neferine in rat liver microsomes showed that the percentage inhibition of the major metabolism （liensinine） formation was 80.5% by quinidine （10 μmol.L^-1, selective CYP2D1 inhibitor） and 25.7% by ketoconazole （1 μmol . L^-1, selective CYP3A1 inhibitor）. Neferine was mainly metabolized by CYP2D1 or CYP3A1 to liensinine, isoliensinine, desmethyl-liensinine and desmethyl-isoliensinine.

关 键 词：甲基莲心碱 高效液相色谱法 液相色谱-串联质谱法 代谢产物 微粒体 

分 类 号：R282.71[医药卫生—中药学] R968.1[医药卫生—中医学]